[Effect of spironolactone on L-arginine/iNOS/NO pathway of aortic adventitia in spontaneously hypertensive rats].

Objective: Adventitia plays an important role in vascular injury diseases. Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is involved in many cardiovascular diseases. iNOS/NO pathway is activated in aorta of spontaneously hypertensive rats (SHRs). The role of aldosterone in L-arginine (L-Arg)/iNOS/NO pathway of aortic adventitia is uncertain. We investigated the effect of aldosterone antagonist spironolactone on adventitial L-Arg/iNOS/NO pathway in SHRs.

Methods: Twenty male SHR (10 weeks old, 220-280 g) were randomly divided into 2 groups (10 in each): untreated or treated with the aldosterone receptor antagonist, spironolactone (20 mg/kg per day) for 6 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as control. Systolic blood pressure (tail-cuff method) was measured weekly. Six weeks later, the rats were sacrificed. The whole aorta was collected and aortic adventitia was isolated. iNOS activity, [(3)H]-L-Arg transport assay of aortic adventitia were carried out by isotope-labeled L-arginine conversion rate measurement, and measurement of nitrate/nitrite (NOx), an index of NO production of aortic adventitia was assayed with the Griess reaction.

Results: iNOS activity, [(3)H]-L-Arg transport and NO production were greatly increased in aortic adventitia of SHR [(12.55 +/- 2.27) pmol x mg(-1) x min(-1), (0.88 +/- 0.19) pmol x mg(-1) x min(-1) and (2.07 +/- 0.39) micromol/L)] compare versus WKY [(5.96 +/- 1.87) pmol x mg(-1) x min(-1), (0.51 +/- 0.15) pmolxmg(-1) x min(-1) and (1.55 +/- 0.32) micromol/L, P < 0.01], and decreased significantly by spironolactone treatment [(8.32 +/- 1.84) pmol x mg(-1) x min(-1), (0.61 +/- 0.15) pmol x mg(-1) x min(-1) and (1.64 +/- 0.27) micromol/L, P < 0.01].

Conclusion: L-Arg/iNOS/NO is activated in aortic adventitia of SHR. Spironolactone can inhibit the activation of L-Arg/iNOS/NO pathway. Aldosterone may play an important role in some cardiovascular diseases such as atherosclerosis through iNOS/NO pathway.